The objectives of the proposed work are to describe the behavioral effects of PCP, define its neurochemical mechanism of action and identify any active metabolites which could account for its long-term behavioral effects in man. An animal model of PCP action will be developed in kittens and cats against which neurochemical events can be evaluated, metabolites can be tested for activity and pharmacological agents can be used to specify sites of PCP action. The effects of PCP will be studied on three transmitter systems, acetylcholine, dopamine, and GABA in the developing kitten, the cat and the rat. The course of transmitter development for the GABAergic system will be delineated so that comparisons can be made with the cholinergic and dopaminergic systems. Behavioral experiments will define the dose and time parameters for assessing neurochemical events in both the acute and chronically treated animal. Pharmacological agents, with recognized mechanisms of action, will be used as tools to further define the site of action of PCP. Metabolites of PCP, identified and synthesized in another project, will also be examined for their behavioral and neurochemical effects to see if they contribute to the pharmacology of the parent drug. This work will assess the formation of active metabolites in the two species studied. The neurochemical measurements will use stable isotope GC/MS procedures for the cholinergic and GABAergic systems and in vivo voltammetry and radio chemical procedures for the dopaminergic system. This project thus proposes a basic neurochemical approach to the actions of a popular drug of abuse. Such studies will provide a fundamental basis for therapeutic intervention in acute situations and, with the metabolite studies, could elucidate the mechanisms in the unpredictable long-term actions of PCP and its congeners.